Millimeter (MM) and TeraHertz (Thz) electromagnetic waves, i.e. waves having a frequency in the range 3×10^10 to 3×10^11 and 10^11 to 10^13 Hz, respectively, can probe various inter- and intra-macromolecular functional properties: biomolecule's and lipid membrane's hydration, binding reactions with other biomolecules, conformational changes and its functioning. This creates new possibilities for real-time, immobilization-free and label-free biosensing of biomolecular entities of different complexity: cells, nucleic acids, proteins, polypeptides, carbohydrates, lipids.
The majority of studies were carried out with specially treated samples in order to overcome the severe attenuation of THz waves by liquids which shadow the biomolecules' response. Pressed pellets, hydrated films and cryogenically frozen samples enable free-space measurements to be carried out on biological samples with a reasonable sensitivity at THz frequencies. A disadvantage of these measurement methods is that the unnatural environment, does not allow investigations of biomolecule's conformational evolution with biological function. Another major drawback with free-space measurements is the necessity for large sample quantities and high-performance equipment such as bright sources or sensitive detectors, which prohibits wide-scale application and commercialization.
Integrated THz sensing approaches have proved to be more sensitive and sample quantity-reducing, but measurements with sufficient hydration still present a challenge. In integrated sensors based on planar transmission lines the sample cannot be loaded at the location of maximum EM field strength, resulting in a large propagation attenuation along the longer transmission line which is required for a longer interaction path length. In the case of a single wire transmission line, the interaction is much stronger. However both planar transmission lines and single wire transmission lines suffer from excessive losses which reduce the measurement sensitivity to dielectric permittivity changes in the sample.
V. Matvejev et al, discloses in “Integrated waveguide structure for highly sensitive THz spectroscopy of nano-liter liquids in capillary tubes”, published in “Progress In Electromagnetics Research” 2011, vol. 121, p 89 to 101, a technique for highly sensitive THz liquid spectroscopy, which is suitable for bio-sensing applications. The sensor consisted of integrated low-loss hexagonal cross-section waveguide comprising a squared opening and a commercially available fused silica capillary tube positioned in this opening.